NR 565 Week 4 Chapter 15: Drugs Affecting the Central Nervous System

Anorexiants (p. 226): Short-term adjuncts to calorie limiting, cognitive-behavioral, weight-loss programs for 

severely obese individuals. Nonamphetamine appetite suppressants are commonly used today but are 

chemically and pharmacologically related to amphetamines. (Phendimetrazine, Benzphetamine, Diethylpropion 

HCl, Phentermine, Lorcaserin) 

Precautions and Contraindications: High risk of tolerance and dependence. Should be used in caution with 

patients who have a history of alcohol or drug dependence. Use should be limited to 6 months and discontinued 

at any sign of tolerance. 

Substance Abuse: Patients who abuse substances such as cocaine, phencyclidine, and methamphetamine 

should not be prescribed anorexiants because of the potential for excessive adrenergic stimulation.

Alcoholics: Actively drinking alcoholics taking anorexiants have experienced depression, paranoia, and 

psychosis.

Diabetes: Patients with diabetes may experiences altered insulin or oral hypoglycemic dosage 

requirements.

Lorcaserin: Serotonergic drug. Patients may develop serotonin syndrome or Neuroleptic Malignant 

Syndrome like reactions if coadministered with serotonergic drugs. Pregnancy Category X and is not 

approved in children under 18.

Anticonvulsants (p. 227): 

Hydantoins: First line treatment of choice for tonic-clonic and partial complex seizures and the lease sedating 

drugs used to treat seizure disorders of any type. (phenytoin-Dilantin, ethotoin-Peganone, fosphenytoinCerebyx). 

Pharmacodynamics: Inhibit and stabilize electrical discharges in the motor cortex of the brain by 

affecting the influx of sodium ions into the neuron during depolarization and repolarization, slowing the 

propagation and spread of abnormal discharges.

Metabolism and Excretion: Metabolism takes place in the liver and excretion via the kidneys. 

Plasma half-lives range from 6-24 hours.

Precautions and Contraindications: Contraindicated under conditions of hypersensitivity. Phenytoin 

induced hepatitis is a common hypersensitivity reaction. Other hypersensitivity reactions include fever, 

rash, arthralgias, and lymphadenopathy. 

Phenytoin: May cause severe cardiovascular events and death has resulted from too-rapid IV 

administration. Phenytoin has a Black-Box Warning that IV administration should not exceed 

50mg/minute in adults and 1-3 mg/kg/minute in pediatric patients owing to risk of cardiovascular 

reactions associated with a too rapid rate of administration. Contraindicated in sinus bradycardia, 

sinoatrial block, second-and third-degree AV block, and Stokes-Adams syndrome. Should be 

used cautiously in patients with hepatic or renal disease. 

Ethotoin: Contraindicated in the presence of hepatic or hematological disorders. 

Fetal Defects: Pregnancy Category D. About 10% of babies have defects in Mother’s who take 

phenytoin during pregnancy. Newborns exposed to phenytoin is utero may experience decreased 

levels of Vitamin K-dependent clotting factors and the mother should receive Vitamin K before 

delivery and the newborn at birth. 

Adverse Drug Reactions: CNS effects (agitation, ataxia, confusion, dizziness, drowsiness, headache, and 

nystagmus), Cardiovascular effects (hypotension, tachycardia, atrial and ventricular conduction 

depression, and ventricular fibrillation), GI effects (nausea, vomiting, anorexia, altered taste, 

constipation, dry mouth, and gingival hyperplasia), GU effects (urinary retention and reddish-brown 

discoloration of urine), Dermatologic reactions (Stevens-Johnson Syndrome and toxic epidermal 

necrolysis). 

Drug Interactions: Interactions that increase hydantoins effect because of increased metabolism, 

competition for binding sites or for unknown reasons occur with benzodiazepines, cimetidine, 

disulfiram, TCAs, salicylates, and valproic acid. Interactions that decrease hydantoin’s effect include 

barbiturates, rifampin, theophylline, influenza vaccine, pyridoxine, and antacids. Oral contraceptives 

effect is decreased with use of hydantoins. Acute alcohol intake may increase phenytoin serum levels, 

whereas chronic alcohol use may decrease levels. IV phenytoin should only be mixed with normal 

saline. 

Monitoring: Patients should be assessed for phenytoin hypersensitivity syndrome (fever, skin rash, 

lymphadenopathy), which usually occurs at 3-8 weeks. Baseline CBC, urinalysis, and LFTs should be 

assessed prior to onset of treatment, with frequent reassessment during the first few months of treatment. 

Plasma levels should be monitored, especially when drugs that increase plasma hydantoin, such as 

ibuprofen, are used. 

Patient Education: Abrupt withdrawal may lead to status epilepticus. Advise the patient to wear a 

medical identification bracelet, to avoid hazardous situations if drowsiness occurs, and to report adverse 

effects to the clinician. Patients should avoid alcohol use. Maintain good oral hygiene to prevent 

tenderness, bleeding, and gingival hyperplasia. Phenytoin may color the urine red, pink, or reddish 

brown but the color change is not a cause for alarm. Advise diabetic patients to monitor blood glucose 

levels and report significant changes to the clinician. 

Iminostilbenes (p. 235): (Carbamazepine-Tegretol and oxcarbazepine-Trileptal). Structurally related to TCAs. 

Used to treat epilepsy, bipolar affective disorder, aggressive and assaultive behavior, and some neuralgias.

Pharmacodynamics: Thought to affect the sodium channels, slowing influx of sodium in the cortical 

neurons and slowing the spread of abnormal activity. Carbamazepine exerts its effect by depressing 

transmission in the nucleus ventralis anterior of the thalamus. This area is associated with the spread of 

seizure discharge. 

Metabolism and Excretion: Carbamazepine is metabolized in the liver and has the unique ability 

to induce its own metabolism (autoinduction). Due to autoinduction, initial concentrations within 

a therapeutic range may later fall despite good compliance. It also induces the metabolism of 

many CYP450 enzymes and other substrates. Excretion is through urine and feces. 

Oxcarbazepine is metabolized into an active metabolite 10-monohydroxy metabolite, which is 

responsible for the pharmacologic effect of the drug. The metabolites of oxcarbazepine are 

excreted 95% in urine, 4% in feces, and 1% unmetabolized oxcarbazepine. 

Precautions and Contraindications: 

Carbamazepine: Contraindications include hypersensitivity to carbamazepine or TCAs, history 

of bone marrow suppression, and current administration with MAOIs. Carbamazepine is 

Pregnancy Category D; tetratogenic defects have occurred including spina bifida. Black-Box 

Warning regarding serious dermatological reactions, particularly among patients of Asian 

ethnicity (Stevens-Johnson Syndrome, toxic epidermal necrolysis and risk of developing aplastic 

anemia and agranulocytosis). Patients of Asian ethnicity should be screened for presence of the 

HLA-B*1502 genetic variant prior to starting carbamazepine. Caution is advised in patients with 

a history of previous adverse hematological reactions to any drugs and in those with cardiac, 

renal, or hepatic impairment. 

Oxcarbazepine: Pregnancy Category C; it crosses the placenta and adverse effects have been 

noted in animal studies. Contraindicated with hypersensitivity to oxcarbazepine. 

Adverse Drug Reactions: Carbamazepine has a Black Box Warning regarding the development of 

Stevens-Johnson Syndrome and toxic epidermal necrolysis in patients of Asian ethnicity. 

Carbamazepine has a Black Box Warning due to its potential to cause blood dyscrasias, some potentially 

lethal. Carbamazepine can depress the bone marrow and lead to leukopenia, thrombocytopenia, 

agranulocytosis, and aplastic anemia. For that reason, a baseline CBC, chemistry, LFTs, and TSH should 

be obtained, followed by periodic monitoring. Follow up studies should be more frequent initially, 

decreasing to every 3-4 months if the results remain normal. Other adverse reactions to carbamazepine 

include hepatic damage and impaired thyroid function. Less serious adverse events include drowsiness, 

dizziness, blurred vision, ataxia, nausea, vomiting, dry mouth, diplopia, and headache. The most 

common adverse effects observed in patients taking oxcarbazepine were dizziness, diplopia, 

somnolence, fatigue, N/V, ataxia, abdominal pain, tremor, and dyspepsia. Hyponatremia may occur, 

particularly in the first 3 months of therapy. 

Drug Interactions:

Carbamazepine: The interactions of most significance are those that increase the plasma level of 

carbamazepine to potentially toxic levels, such as the concurrent administration of 

propoxyphene, hydantoins, cimetidine, some Abx (erythromycin, clarithromycin), isoniazid, and 

verapamil. Interactions that decrease plasma levels of the other drug occur with beta blockers, 

succinimides, valproic acid, warfarin, haloperidol, doxycycline, and nondepolarizing muscle 

relaxants. Grapefruit juice increases serum levels and effects of carbamazepine. 

Oxcarbazepine: Can inhibit CYP2C19 and induce CYP3A4/5, leading to increased levels of 

drugs metabolized by CYP2C19. May decrease effectiveness of contraceptives containing 

ethinylestradiol and levonorgestrel.